tbuckley/cabot-search huggingface dataset:
A scenario modelling analysis to anticipate the impact of COVID-19 vaccination in adolescents and children on disease outcomes in the Netherlands, summer 2021
Authors: Kylie E C Ainslie, Jantien A Backer, Pieter T de Boer, Albert Jan van Hoek, Don Klinkenberg, Hester Korthals Altes, Ka Yin Leung, Hester de Melker, Fuminari Miura, Jacco Wallinga
Journal: Eurosurveillance (2022)

Background Since the roll-out of COVID-19 vaccines in late 2020 and throughout 2021, European governments have relied on mathematical modelling to inform policy decisions about COVID-19 vaccination. Aim We present a scenario-based modelling analysis in the Netherlands during summer 2021, to inform whether to extend vaccination to adolescents (12–17-year-olds) and children (5–11-year-olds). Methods We developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model and compared modelled incidences of infections, hospital and intensive care admissions, and deaths per 100,000 people across vaccination scenarios, before the emergence of the Omicron variant. Results Our model projections showed that, on average, upon the release of all non-pharmaceutical control measures on 1 November 2021, a large COVID-19 wave may occur in winter 2021/22, followed by a smaller, second wave in spring 2022, regardless of the vaccination scenario. The model projected reductions in infections/severe disease outcomes when vaccination was extended to adolescents and further reductions when vaccination was extended to all people over 5 years-old. When examining projected disease outcomes by age group, individuals benefitting most from extending vaccination were adolescents and children themselves. We also observed reductions in disease outcomes in older age groups, particularly of parent age (30–49 years), when children and adolescents were vaccinated, suggesting some prevention of onward transmission from younger to older age groups. Conclusions While our scenarios could not anticipate the emergence/consequences of SARS-CoV-2 Omicron variant, we illustrate how our approach can assist decision making. This could be useful when considering to provide booster doses or intervening against future infection waves.
Metabolomic, Lipidomic, Transcriptomic, and Metagenomic Analyses in Mice Exposed to PFOS and Fed Soluble and Insoluble Dietary Fibers
Authors: Pan Deng, Jerika Durham, Jinpeng Liu, Xiaofei Zhang, Chi Wang, Dong Li, Taesik Gwag, Murong Ma, Bernhard Hennig
Journal: Environmental Health Perspectives (2022)

Background: Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant that has become a significant concern around the world. Exposure to PFOS may alter gut microbiota and liver metabolic homeostasis in mammals, thereby increasing the risk of cardiometabolic diseases. Diets high in soluble fibers can ameliorate metabolic disease risks. Objectives: We aimed to test the hypothesis that soluble fibers (inulin or pectin) could modulate the adverse metabolic effects of PFOS by affecting microbe-liver metabolism and interactions. Methods: Male C57BL/6J mice were fed an isocaloric diet containing different fibers: a) inulin (soluble), b) pectin (soluble), or c) cellulose (control, insoluble). The mice were exposed to PFOS in drinking water (3μg/g per day) for 7 wk. Multi-omics was used to analyze mouse liver and cecum contents. Results: In PFOS-exposed mice, the number of differentially expressed genes associated with atherogenesis and hepatic hyperlipidemia were lower in those that were fed soluble fiber than those fed insoluble fiber. Shotgun metagenomics showed that inulin and pectin protected against differences in microbiome community in PFOS-exposed vs. control mice. It was found that the plasma PFOS levels were lower in inulin-fed mice, and there was a trend of lower liver accumulation of PFOS in soluble fiber-fed mice compared with the control group. Soluble fiber intake ameliorated the effects of PFOS on host hepatic metabolism gene expression and cecal content microbiome structure. Discussions: Results from metabolomic, lipidomic, and transcriptomic studies suggest that inulin- and pectin-fed mice were less susceptible to PFOS-induced liver metabolic disturbance, hepatic lipid accumulation, and transcriptional changes compared with control diet-fed mice. Our study advances the understanding of interaction between microbes and host under the influences of environmental pollutants and nutrients. The results provide new insights into the microbe-liver metabolic network and the protection against environmental pollutant-induced metabolic diseases by high-fiber diets. https://doi.org/10.1289/EHP11360
Oxidized thioredoxin-1 restrains the NLRP1 inflammasome
Authors: Daniel P. Ball, Lydia P. Tsamouri, Alvin E. Wang, Hsin-Che Huang, Charles D. Warren, Qinghui Wang, Isabelle H. Edmondson, Andrew R. Griswold, Sahana D. Rao, Darren C. Johnson, Daniel A. Bachovchin
Journal: Science Immunology (2022)

The danger signals that activate the NLRP1 inflammasome have not been established. Here, we report that the oxidized, but not the reduced, form of thioredoxin-1 (TRX1) binds to NLRP1. We found that oxidized TRX1 associates with the NACHT-LRR region of NLRP1 in an ATP-dependent process, forming a stable complex that restrains inflammasome activation. Consistent with these findings, patient-derived and ATPase-inactivating mutations in the NACHT-LRR region that cause hyperactive inflammasome formation interfere with TRX1 binding. Overall, this work strongly suggests that reductive stress, the cellular perturbation that will eliminate oxidized TRX1 and abrogate the TRX1-NLRP1 interaction, is a danger signal that activates the NLRP1 inflammasome.
Efficacy of tixagevimab-cilgavimab in preventing SARS-CoV-2 for patients with B-cell malignancies
Authors: James A. Davis, Katelynn Granger, Kiera Roubal, Deidra Smith, Kelly J. Gaffney, Mary McGann, Alyssa Cendagorta, Aswani Thurlapati, Amanda Herbst, Lindsey Hendrickson, Hamza Hashmi, Brian T. Hess
Journal: Blood (2022)
FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study
Authors: Shengbing Zhao, Shuling Wang, Peng Pan, Tian Xia, Rundong Wang, Quancai Cai, Xin Chang, Fan Yang, Lun Gu, Zixuan He, Jiayi Wu, Qianqian Meng, Tongchang Wang, Qiwen Fang, Xiaomei Mou, Honggang Yu, Jinghua Zheng, Cheng Bai, Yingbin Zou, Dongfeng Chen, Xiaoping Zou, Xu Ren, Leiming Xu, Ping Yao, Guangsu Xiong, Xu Shu, Tong Dang, Li Zhang, Wen Wang, Shengchao Kang, Hongfei Cao, Aixia Gong, Jun Li, Heng Zhang, Yiqi Du, Zhaoshen Li, Yu Bai
Journal: Journal of Hematology & Oncology (2022)

Abstract No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation ( n = 6776) or validation cohort ( n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0–14), intermediate risk (IR 15–17), and high risk (HR 18–28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P &lt; 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P &lt; 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.
Correction: Identification of novel HLA-A*11:01-restricted HPV16 E6/E7 epitopes and T-cell receptors for HPV-related cancer immunotherapy
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background: E6 and E7 oncoproteins are considered ideal antigens of T cell therapy for human papillomavirus (HPV)-related cancers.However, little is known about the epitopes of E6 and E7 presented by HLA-A*11:01, one of the most prevalent HLA types globally, especially in Asia.Methods: We combined in silico and experimental approaches to identify endogenously processed HLA-A*11:01-restricted epitopes of HPV16 E6 and E7.The identified epitopes were then used to screen available T cell receptors (TCRs) from healthy donors through in vitro stimulation of peripheral blood mononuclear cells (PBMCs).Results: E693-101 (TTLEQQYNK, TTL) and E789-97 (IVCPICSQK, IVC), two novel HLA-A*11:01-restricted T cell epitopes of HPV16, were identified to be endogenously presented on tumor cells.TTL-and IVC-specific TCRs were isolated from 11 healthy donors through in vitro stimulation of PBMC.The key TTL and IVC residues involved in TCR-pMHC interactions were mapped, and the consensus sequence was "xxLE-QxYNK" and "xVxPIxxxK."The TTL-and IVC-specific TCRs with high functional avidity were used to generate TCR-engineered T cells, specifically recognizing and killing corresponding tumor cell lines in vitro and in vivo.In addition, TTL and IVCspecific TCR-T cells also recognized and killed HPV16+patient-derived organoids. Conclusions:The HLA-A*11:01-restricted HPV16 E6/E7 epitopes and TCRs identified in this study may provide a new strategy for HPV-related cancer immunotherapy in HLA-A*11:01+patients.
Gutsy memory T cells stand their ground against pathogens
Authors: Isaac J. Jensen, Donna L. Farber
Journal: Science Immunology (2022)

Elegant fate-mapping models to label intestinal tissue-resident memory CD8+ T (TRM) cells demonstrate retention and lack of expansion of CD103+ TRM cells, whereas intestinal CD103- memory cells expand, forming both new tissue-localized CD103+ and CD103- TRM cells (see related Research Articles by Fung et al. and von Hoesslin et al.).
Achieving a Cure Without Total Mesorectal Excision in Rectal Adenocarcinoma
Authors: William A. Hall, J. Joshua Smith
Journal: Journal of Clinical Oncology (2022)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. Rectal cancer is a curable disease, yet curing the disease can be associated with lifelong morbidity because of the nature of the curative-intent treatment strategies. A major focus of modern prospective trials has been to maintain current cure rates, while minimizing lifelong lifestyle alterations and maximizing quality of life. Navigating the complex landscape of therapeutic options for rectal adenocarcinoma with a focus to accomplish this quality-of-life improvement is a critical focus area for future clinical trials. Many challenges remain on the path to optimizing cure and minimizing morbidity, and include improving initial staging accuracy, more precise selection of neoadjuvant therapy used for each patient, choosing the optimal surgical management strategy, and ensuring modern radiation therapy approaches are being used. Finally, organ preservation strategies have moved to the forefront in the management of both early and locally advanced rectal cancers and hold the potential for significant changes to come for patients with rectal cancer. Herein, we highlight some of the challenges remaining in the field, progress made, and how the recent data from the Canadian Cancer Trials Group phase II trial can be put into context with the ACOSOG Z6041, CARTS, and GRECCAR2 trials.
Secondary infections rejuvenate the intestinal CD103 <sup>+</sup> tissue-resident memory T cell pool
Authors: Madlaina von Hoesslin, Miriam Kuhlmann, Gustavo Pereira de Almeida, Kristiyan Kanev, Christine Wurmser, Ann-Katrin Gerullis, Patrick Roelli, Jacqueline Berner, Dietmar Zehn
Journal: Science Immunology (2022)

Resident T lymphocytes (T RM ) protect tissues during pathogen reexposure. Although T RM phenotype and restricted migratory pattern are established, we have a limited understanding of their response kinetics, stability, and turnover during reinfections. Such characterizations have been restricted by the absence of in vivo fate-mapping systems. We generated two mouse models, one to stably mark CD103 + T cells (a marker of T RM cells) and the other to specifically deplete CD103 − T cells. Using these models, we observed that intestinal CD103 + T cells became activated during viral or bacterial reinfection, remained organ-confined, and retained their original phenotype but failed to reexpand. Instead, the population was largely rejuvenated by CD103 + T cells formed de novo during reinfections. This pattern remained unchanged upon deletion of antigen-specific circulating T cells, indicating that the lack of expansion was not due to competition with circulating subsets. Thus, although intestinal CD103 + resident T cells survived long term without antigen, they lacked the ability of classical memory T cells to reexpand. This indicated that CD103 + T cell populations could not autonomously maintain themselves. Instead, their numbers were sustained during reinfection via de novo formation from CD103 − precursors. Moreover, in contrast to CD103 - cells, which require antigen plus inflammation for their activation, CD103 + T RM became fully activated follwing exposure to inflammation alone. Together, our data indicate that primary CD103 + resident memory T cells lack secondary expansion potential and require CD103 − precursors for their long-term maintenance.
Should We Aspire to Be Rational About Letting Babies Die?
Authors: John D. Lantos
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Postponed Withholding: An Ethical Tool for Health Care Personnel to Empower ParentsThis article refers to:Postponed Withholding: Balanced Decision-Making at the Margins of Viability Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Deferring Decision-making in the Face of Uncertainty
Authors: Dominic J. C. Wilkinson
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Postponed Withholding: An Ethical Tool for Health Care Personnel to Empower ParentsThis article refers to:Postponed Withholding: Balanced Decision-Making at the Margins of Viability Additional informationFundingThis research was funded in part by the Wellcome Trust [203132/Z/16/Z]. The funders had no role in the preparation of this manuscript or the decision to submit for publication.
Postponed Withholding: Harmful for the Infant and Increasing the Complexity of Decision-Making
Authors: Lien De Proost, Eline Bunnik, Angret de Boer, E. J (Joanne) Verweij
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Postponed Withholding: An Ethical Tool for Health Care Personnel to Empower ParentsThis article refers to:Postponed Withholding: Balanced Decision-Making at the Margins of Viability DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingZonMW: On the limits of perinatal viability: ethical challenges of personalized counseling and the artificial placenta [40-00703-97-19039], and MRACE Erasmus MC.
Against Multiplying Clinical Ethics Standards without Necessity: The Case for Parsimony in Evaluating Decision-making Capacity
Authors: Jeremy R. Garrett, John C. Moskop, J. Clint Parker
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Capacities to Refuse Treatment: A ReplyThis article refers to:Three Kinds of Decision-Making Capacity for Refusing Medical Interventions Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Postponed Withholding Does Not Postpone Attachment
Authors: Brian S. Carter
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Postponed Withholding: An Ethical Tool for Health Care Personnel to Empower ParentsThis article refers to:Postponed Withholding: Balanced Decision-Making at the Margins of Viability Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
What Is the Ethical Goal of Empowering Parents in Emergent Decision-making about Their Premature Newborn?
Authors: Lynn Gillam, Trisha M. Prentice
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Postponed Withholding: An Ethical Tool for Health Care Personnel to Empower ParentsThis article refers to:Postponed Withholding: Balanced Decision-Making at the Margins of Viability Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Emerging approaches to redressing multi-level racism and reproductive health disparities
Authors: Bethany Golden, Ifeyinwa V. Asiodu, Linda S. Franck, Celestine Yayra Ofori-Parku, Daniel Felipe Martín Suárez-Baquero, Tracy Youngston, Monica R. McLemore
Journal: npj Digital Medicine (2022)

This commentary examines the impact of multi-level racism on reproductive health disparities in the United States. Multi-level racism and its impact on reproductive health over the lifespan are described on a societal, community, and individual level. To advance, we recommend using the Remove, Repair, Restructure, Remediate (R4P) approach combined with the Retrofit, Reform, and Reimagine (3R) model to address multiple forms of racism. Emergent policies and actions are identified to proceed towards health equity.
Supported Decision Making, Treatment Refusal, and Decisional Capacity
Authors: Megan S. Wright
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Capacities to Refuse Treatment: A ReplyThis article refers to:Three Kinds of Decision-Making Capacity for Refusing Medical Interventions Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Use Certified Patient Decision Aids to Facilitate Shared Decision Making at the Margins of Viability
Authors: Thaddeus Mason Pope
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Postponed Withholding: An Ethical Tool for Health Care Personnel to Empower ParentsThis article refers to:Postponed Withholding: Balanced Decision-Making at the Margins of Viability Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Why Not Jump out of Decision-Making Capacity?
Authors: Yali Cong
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Capacities to Refuse Treatment: A ReplyThis article refers to:Three Kinds of Decision-Making Capacity for Refusing Medical Interventions DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author acknowledges the support from China-US Center for Medical Professionalism, Peking University Health Science Center.
OrganEx: What Will It Mean?
Authors: Henry T. Greely
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image size ACKNOWLEDGMENTSI would like to thank Patti Zettler and David Magnus for helpful suggestions. I played a role in providing ethical advice to an earlier, related project by Dr. Sestan, the BrainEx experiments. I was not involved in any way in the OrganEx experiment.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Delayed Withholding: Disguising Withdrawal of Life Sustaining Interventions in Extremely Preterm Infants
Authors: Annie Janvier, Keith J. Barrington
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Postponed Withholding: An Ethical Tool for Health Care Personnel to Empower ParentsThis article refers to:Postponed Withholding: Balanced Decision-Making at the Margins of Viability Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Reformulating Decision-making Capacity
Authors: Simon Walker, Otis Williams, Giles Newton-Howes, Neil Pickering
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article is referred to by:Capacities to Refuse Treatment: A ReplyThis article refers to:Three Kinds of Decision-Making Capacity for Refusing Medical Interventions Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
Postponed Withholding: An Ethical Tool for Health Care Personnel to Empower Parents
Authors: Janicke Syltern, Lars Ursin, Berge Solberg, Ragnhild Støen
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article refers to:Postponed Withholding: Balanced Decision-Making at the Margins of ViabilityInformed Nondissent at the Limits of ViabilityDeferring Decision-making in the Face of UncertaintyPostponed Withholding: The Wrong NudgePostponed Withholding: Harmful for the Infant and Increasing the Complexity of Decision-MakingUse Certified Patient Decision Aids to Facilitate Shared Decision Making at the Margins of ViabilityDefault Withdrawal: Exacerbating Mistrust for Our Most Vulnerable FamiliesThe Birth of Tragedy? Extremely Premature Births and Shared Decision-MakingEmbrace the Gray: How Tackling the Clinical Complexities of the Gray Zone Will Improve Decision-makingThe Postponed Withholding Model: An Autoethnographic AnalysisShould We Aspire to Be Rational About Letting Babies Die?The Path More Easily Reversed: Postponed Withholding at Borderline ViabilityDelayed Withholding: Disguising Withdrawal of Life Sustaining Interventions in Extremely Preterm InfantsPostponed Withholding Does Not Postpone AttachmentWhat Is the Ethical Goal of Empowering Parents in Emergent Decision-making about Their Premature Newborn? Additional informationFundingThis work was supported by The Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, Trondheim, Norway [SO: 90278900b].